Are all SGLT2 Inhibitors Created Equal?

Sodium/glucose cotransporter 2 (SGLT2) inhibitors have rapidly become a cornerstone of heart failure (HF) drug therapy. Both dapagliflozin and empagliflozin have proven effective in preventing cardiovascular death and hospitalization for HF in patients regardless of background ejection fraction.

A class-effect exists for most drugs in HF, and any angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blockers (ARBs), for example, can be used for HF. However, there are some instances where certain drugs within a class are more effective than others. Take beta-blockers, for instance. Carvedilol was proven superior to metoprolol tartrate in treating patients with HF.

To date, SGLT2 inhibitors have only been studied against placebos. In this installment of Talking Therapeutics, we explore a new study that evaluates dapagliflozin against empagliflozin in patients with HF.

Talking Point: Signal for Superiority

Included patients were identified from the TriNetX Research Collaborative Network database of 81 health care organizations. Patients treated with empagliflozin-treated were designated as the intervention group and those receiving dapagliflozin were the comparator group. The primary outcome was the composite of all-cause mortality or hospitalization from day zero (eg, first day of SGLT2 inhibitor treatment) through 1-year follow-up.

After propensity-matching for demographics, diagnoses, and medication use, there were 11 077 in each group. Patients treated with empagliflozin-treated were less likely to experience the primary composite outcome of all-cause mortality or hospitalization compared to those treated with dapagliflozin, 3545 (32.2%) vs 3828 (34.8%) events (HR, 0.90; 95% CI, 0.86-0.94) within 1 year of SGLT2 inhibitor initiation. This difference was primarily driven by a lower rate of hospitalization with empagliflozin compared to dapagliflozin (HR, 0.90; 95% CI, 0.86-0.94).

Talking Point: More Data Needed

These data are certainly provocative; however, we cannot form definitive conclusions about the superiority of empagliflozin over dapagliflozin without a head-to-head randomized trial. Given that this study was a nonrandomized database analysis, there is too much potential confounding to draw firm conclusions.

On the other hand, dapagliflozin and empagliflozin are very similar drugs. Similar side effects, drug-interactions, and cost. Given that they are so similar, there are no theoretical downsides that I can muster to preferentially using one over the other. As such, I will likely be preferentially using empagliflozin over dapagliflozin going forward as we await further data.